Pooled serum proteomic profiling reveals shared and distinct molecular features in nonerosive reflux disease and reflux esophagitis: A retrospective observational study.

ObjectiveGastroesophageal reflux disease comprises heterogeneous phenotypes, and symptom severity does not always correlate with endoscopic findings. This retrospective observational study aimed to characterize serum proteomic alterations in gastroesophageal reflux disease and to explore whether nonerosive reflux disease and reflux esophagitis exhibit distinct circulating protein signatures.MethodsSeventy individuals were included, comprising 26 controls, 14 patients with nonerosive reflux disease, and 30 with reflux esophagitis. For exploratory group-level proteomic discovery, pooled serum samples from each group were analyzed using liquid chromatography-tandem mass spectrometry. Clinical characteristics, upper gastrointestinal endoscopy, high-resolution manometry, and 24-h pH-impedance monitoring were assessed as appropriate. Differentially expressed proteins were identified using a fold change threshold of 1.3 together with nominal statistical significance, followed by functional annotation and enrichment analyses.ResultsAge and sex were comparable among the groups. Nonerosive reflux disease and reflux esophagitis showed no significant differences in gastroesophageal reflux disease questionnaire score, disease duration, body mass index, or most reflux-monitoring parameters. However, patients with reflux esophagitis had more gas reflux episodes, lower distal contractile integral values, and a higher frequency of esophageal motility disorders, suggesting impaired motor function. Proteomic profiling identified 872 proteins, including 666 quantified proteins. Differential expression analysis identified 48 proteins in nonerosive reflux disease versus controls, 43 in reflux esophagitis versus controls, and 7 in nonerosive reflux disease versus reflux esophagitis. The exploratory nonerosive reflux disease-associated protein profile was mainly characterized by cytoskeletal remodeling, adhesion-related regulation, redox adaptation, and selective immune rearrangement, whereas the exploratory reflux esophagitis-associated profile showed features related to actin remodeling, injury-defense responses, and alterations in lipid homeostasis.ConclusionsNonerosive reflux disease and reflux esophagitis exhibited distinct but partially overlapping serum proteomic profiles in this exploratory pooled serum analysis. These preliminary findings suggest phenotype-related biological differences beyond reflux burden alone; however, they should be interpreted as hypothesis-generating and require validation in independent, individual-level cohorts.